The SNP rs1800497 in the DRD2 gene has been associated with a reduction in the density of type 2 dopamine receptors in the presynaptic membrane of the mesolimbic pathways, causing an increase in dopamine concentration contributing to behavior of abuse and compulsion [13]. The SNP rs6265 in the BDNF gene decreases the production of neurotrophins that acts in the hypothalamus and stimulates hormones related to satiety, such as TRH and CRH [11]. Interestingly, in the present study, the SNP rs1800497 in the DRD2 gene and the SNP rs6265 in the BDNF gene were more frequent in patients with BED, corroborating with previous studies, which also found an association between these polymorphisms and BED [10, 22–23].
Especially for the SNP rs1800497 in the DRD2 gene, studies have demonstrated reduced dopamine function in the brain [24–25], about 30 to 40% of the normal value [5]. In addition, this polymorphism was linked to increased BMI and eating disorders in women with bulimia spectrum disorder [26–27], which is considered a possible marker for the high risk of developing pathological eating behavior [28]. Other studies showed that the presence of the T allele for the DRD2 gene is associated with unhealthy eating, abnormal levels of glucose and triglycerides [29], other addictive behaviors combined with overweight [30], obesity [31], hedonic diet [32], and high sensitivity to reward [33]. All these factors directly influence the increase in caloric intake [34] favored by facilitated access to highly palatable and caloric foods [22].
The presence of the SNP rs6265 in the BDNF gene has been associated with obesity [12, 36] and overweight in childhood [37–39]. The present study showed a predominance of a variant allele (GA + AA) in individuals with BED (p = 0.025), revealing that the presence of the A allele can be an aggravating factor for BED. Another study involving three groups of female patients (bulimia nervosa, BED, and healthy controls) revealed that in the BED group, individuals with the AA genotype exhibited a significantly greater severity of binge eating [40]. In another study, the interaction between the rs6265 SNP and sex indicated that men with the GG genotype had higher BMI, waist circumference, and weight than those with GA or AA genotypes. Nonetheless, women with the GG genotype had a significantly lower BMI than those with GA or AA genotypes. According to the authors, the rs6265 SNP in the BDNF gene is associated with an increased risk of obesity in a sex manner [12]. In the present study, we did not analyze the predominance of the genotype between the sexes due to the higher prevalence of females in the sample.
The analysis combining genotypes of the two studied polymorphisms revealed that polymorphism rs1800497 in the DRD2 gene and the polymorphism rs6265 in the BDNF gene were predominant in the BED group. The literature evaluating the combination of these polymorphisms and BED is scarce. However, given the data obtained in this study, a possible synergism could occur between these genetic variants potentiating the predisposition to develop BED disorders [30, 40, 44, 45].
Weight regain was present in both groups of obese patients with and without BED. However, there was no difference in the mean BMI between the groups for each studied genotype. The literature on weight regains for the polymorphisms studied is limited. Perkovic et al., 2013 did not find an association between SNP rs6265 and weight gain throughout the life of patients followed from 40 to 70 years of age [46]. In addition, a study that followed 1406 patients for more than six years after bariatric surgery revealed that more than 67% of patients recover 20% or more of the lost weight in the first two years [47–48]. In this context, obesity is characterized as a multifactorial disease, and the evidence presented by the literature indicates that even after different types of treatments for weight loss (surgical or not), a weight regain could occur over the years. Thus, several factors, including genetics, can act for this "new" weight gain after treatments.
The strength of this study is the significant association of the evaluated polymorphisms and BED. The literature addressing this association is scarce, and in the present study, even with a reduced sample, it was possible to observe this effect. In addition, the absence of a non-obese group could also be considered a limitation. Also, the correction for ethnicity could not be applied due to our study considered an admixed population.